Functions of the N-type Ca Channel/14-3-3 Interaction
N型Ca通道的功能/14-3-3相互作用
基本信息
- 批准号:7486997
- 负责人:
- 金额:$ 28.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-01 至 2012-03-31
- 项目状态:已结题
- 来源:
- 关键词:14-3-3 ProteinsAffectAntibodiesBindingBiochemicalBrainCalciumCell physiologyChemicalsCommunicationComplexDominant-Negative MutationFamilyGoalsHandHippocampus (Brain)IndividualKineticsKnock-in MouseLocationMediatingMental DepressionMolecularN DomainNerveNervous system structureNeuronsPhosphorylationPlayPropertyProteinsRegulationRoleSynaptic TransmissionSynaptic plasticitySystemTechniquesTestingTimeWorkbasecalmodulin-dependent protein kinase IImutantneurophysiologyneurotransmitter releasenovelpresynapticprotein protein interactionresearch studyvoltage
项目摘要
DESCRIPTION (provided by applicant): The N-type Ca channel, along with the P/Q-type, plays a central role in chemical synaptic transmissions in the nervous system. As these Ca2+ channels determine the amount, timing and location of Ca2+ influx at nerve terminals, changes in Ca2+ channel biophysical properties, especially their inactivation kinetics, can profoundly affect the temporal dynamics of evoked neurotransmitter release. Despite recent advances, there are still major gaps in our understanding of molecular mechanism for Ca2+ channel inactivation, as well as their regulations by signally proteins in neurons. This proposal seeks to understand the cellular and molecular mechanisms of regulation of N-type Ca2+ channels by 14-3-3 proteins, a family of brain-rich proteins that participate in multiple cellular processes. In our preliminary studies, we not only discovered and characterized the novel protein-protein interaction between the N-type Ca2+ channel and 14-3-3, but also determined a profound modulation of inactivation properties of N-type Ca2+ channels by 14-3-3. Furthermore, we revealed a significant change in short-term synaptic plasticity by antagonizing 14-3-3 binding in the presynaptic neuron. In this application, we will build on these findings and further investigate the function and mechanism of this regulatory complex using a combination of molecular, biochemical and electrophysiological techniques. Our specific aims are: (1) Determine the mechanism underlying 14-3-3-dependent modulation of N-type Ca2+ channel inactivation. Specifically, we will investigate whether 14-3-3 modulates inactivation properties of N-type Ca2+ channels through its binding to the channel. (2) Determine the mechanism underlying 14-3-3- dependent modulation of short-term synaptic plasticity. Specifically, we will investigate whether 14-3-3 regulates short-term plasticity by modulating N-type Ca2+ channel inactivation. (3) Determine dynamic interactions between 14-3-3 and N-type Ca2+ channels in neurons. Specifically, we will investigate whether formation of this protein complex is promoted by recurring presynaptic activity, via enhancing CaMKII-dependent phosphorylation of the N-type Ca2+ channel. Together, these studies will provide a novel mechanism for regulation of N-type Ca2+ channels and help to understand 14-3-3's functions in the nervous system.
描述(由申请人提供):N型钙通道,沿着P/Q型钙通道,在神经系统的化学突触传递中起中心作用。由于这些Ca 2+通道决定了神经末梢Ca 2+内流的量、时间和位置,因此Ca 2+通道生物物理性质的变化,特别是其失活动力学,可以深刻地影响诱发神经递质释放的时间动力学。尽管最近取得了进展,但我们对Ca 2+通道失活的分子机制以及神经元中信号蛋白对其的调控仍存在重大差距。该提案旨在了解14-3-3蛋白调节N型Ca 2+通道的细胞和分子机制,14-3-3蛋白是参与多种细胞过程的脑丰富蛋白质家族。在我们的初步研究中,我们不仅发现并表征了N型Ca 2+通道和14-3-3之间的新型蛋白质-蛋白质相互作用,而且确定了14-3-3对N型Ca 2+通道失活特性的深刻调节。此外,我们揭示了一个显着的变化,在短期突触可塑性拮抗14-3-3结合在突触前神经元。在本申请中,我们将建立在这些发现的基础上,并进一步研究这种调节复合物的功能和机制,使用分子,生物化学和电生理技术的组合。我们的具体目标是:(1)确定14-3-3依赖性调节N型Ca ~(2+)通道失活的机制。具体而言,我们将研究14-3-3是否通过其与通道的结合来调节N型Ca 2+通道的失活特性。(2)确定短期突触可塑性的14-3-3依赖性调节的潜在机制。具体而言,我们将研究14-3-3是否通过调节N型Ca 2+通道失活来调节短期可塑性。(3)确定神经元中14-3-3和N型Ca 2+通道之间的动态相互作用。具体来说,我们将调查是否形成这种蛋白质复合物是促进反复突触前活动,通过增强CaMKII依赖磷酸化的N型钙离子通道。总之,这些研究将为N型钙通道的调节提供一种新的机制,并有助于了解14-3-3在神经系统中的功能。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
YI ZHOU其他文献
YI ZHOU的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('YI ZHOU', 18)}}的其他基金
Molecular, synaptic and circuit basis for 14-3-3 dysfunction-induced behavioral deficits
14-3-3 功能障碍引起的行为缺陷的分子、突触和回路基础
- 批准号:
9425032 - 财政年份:2017
- 资助金额:
$ 28.94万 - 项目类别:
Molecular, synaptic and circuit basis for 14-3-3 dysfunction-induced behavioral deficits
14-3-3 功能障碍引起的行为缺陷的分子、突触和回路基础
- 批准号:
10212908 - 财政年份:2017
- 资助金额:
$ 28.94万 - 项目类别:
Functions of the N-type Ca Channel/14-3-3 Interaction
N型Ca通道的功能/14-3-3相互作用
- 批准号:
8046337 - 财政年份:2007
- 资助金额:
$ 28.94万 - 项目类别:
Functions of the N-type Ca Channel/14-3-3 Interaction
N型Ca通道的功能/14-3-3相互作用
- 批准号:
7596209 - 财政年份:2007
- 资助金额:
$ 28.94万 - 项目类别:
Functions of the N-type Ca Channel/14-3-3 Interaction
N型Ca通道的功能/14-3-3相互作用
- 批准号:
7800933 - 财政年份:2007
- 资助金额:
$ 28.94万 - 项目类别:
Functions of the N-type Ca Channel/14-3-3 Interaction
N型Ca通道的功能/14-3-3相互作用
- 批准号:
7212499 - 财政年份:2007
- 资助金额:
$ 28.94万 - 项目类别:
Core C - FACS and Epigenetics Technology Core
核心C - FACS和表观遗传学技术核心
- 批准号:
8565741 - 财政年份:1997
- 资助金额:
$ 28.94万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 28.94万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 28.94万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 28.94万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 28.94万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 28.94万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 28.94万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 28.94万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 28.94万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 28.94万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 28.94万 - 项目类别:
Studentship